PROJECT SUMMARY/ ABSTRACT The human immunodeficiency virus (HIV) prevalence in the Irkutsk, Siberia region is higher than any other in the Russian Federation. Tuberculosis (TB) is the leading killer worldwide of people living with HIV and is simply ravaging Irkutsk. Polysubstance abuse affects multiple aspects of the HIV/TB care continuum in Irkutsk contributing to overwhelming HIV/TB mortality. Despite patients initiating antiretroviral and anti-TB therapy, our data suggests that HIV/TB treatment failure represents the interplay of host nonadherence to complex medication regimens and functional drug-resistance due to suboptimal but correctable anti-TB medication concentrations. Therefore, this project seeks to understand the prospective influence of substance use patterns on adherence, pharmacokinetics and disease progression in the Irkutsk context. We have developed innovative methods for measurement of these factors including mobile phone (mHealth) enhanced ecological momentary assessment of adherence and substance use, urine based medication concentration assays, and mycobacterial DNA detection from the urine as a non-invasive biomarker of disease. This project builds upon our prior US/Russian research collaboration while uniting experts with complimentary and multidisciplinary experience in Behavioral Science, Clinical Psychology, HIV Medicine, mHealth, Pharmacokinetics, HIV/TB coinfection, HIV and TB Drug-Resistance and TB Biomarkers. We expect completion of the project to generate targeted interventions to interrupt the cycle of substance use, HIV and TB in Irkutsk, foster integration of services, and shift HIV care toward a patient-centered model.